MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

Liu, Chang Mei; Wang, Rui Ying; Saijilafu,; Jiao, Zhong Xian; Zhang, Bo Yin; Zhou, Feng

doi:10.1101/gad.209619.112

Cited by 145 publications

(117 citation statements)

References 44 publications

(59 reference statements)

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“…31,32 Cellular NAD depletion and reduced SIRT1 activity were shown to play critical roles in poly (ADP-ribose) polymerase 1-mediated epileptic neuronal death in a hippocampal neuronal culture model of acute acquired epilepsy. 16 Of interest, several studies reported that the SIRT1 activator resveratrol exerted neuroprotective and SE-easing effects. 33 However, the mechanisms regulating SIRT1 in epilepsy have not yet been determined.…”

Section: Discussionmentioning

confidence: 99%

“…13 Recent studies have suggested that SIRT1 is an important endogenous apoptosis inhibitor in neurodegenerative disease, 14,15 and several studies have demonstrated that SIRT1 promotes mammalian axon regeneration and supports neurite outgrowth. 16 The miRNA miR199a has been found to target SIRT1 directly. 17 Given the importance of neurite outgrowth and axon regeneration in epilepsy, we therefore explored the role of the miR-199a/ SIRT1 axis in epilepsy.…”

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confidence: 99%

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Targeting of microRNA‐199a‐5p protects against pilocarpine‐induced status epilepticus and seizure damage via SIRT1‐p53 cascade

Wang

Zhang

et al. 2016

Epilepsia

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SUMMARYObjective: MicroRNAs (miRNAs) are noncoding small RNAs that control gene expression at the posttranscriptional level. Some dysregulated miRNAs have been shown to play important roles in epileptogenesis. The aim of this study was to determine if miR199a-5p regulates seizures and seizure damage by targeting the antiapoptotic protein silent information regulator 1 (SIRT1). Methods: Hippocampal expression levels of miR-199a-5p, SIRT1, and acetylated p53 were quantified by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting in the acute, latent, and chronic stages of epilepsy in a rat lithiumpilocarpine epilepsy model. Silencing of miR-199a-5p expression in vivo was achieved by intracerebroventricular injection of antagomirs. The effects of targeting miR-199a-5p and SIRT1 protein on seizure and epileptic damage post-status epilepticus were assessed by electroencephalography (EEG) and immunohistochemistry, respectively. Results: miR-199a-5p expression was up-regulated, SIRT1 levels were decreased, and neuron loss and apoptosis were induced in epilepsy model rats compared with normal controls, as determined by up-regulation of acetylated p53 and cleaved caspase-3 expression. In vivo knockdown of miR-199a-5p by an antagomir alleviated the seizurelike EEG findings and protected against neuron damage, in accordance with up-regulation of SIRT1 and subsequent deacetylation of p53. Furthermore, the seizure-suppressing effect of the antagomir was partly SIRT1 dependent. Significance: The results of this study suggest that silencing of miR-199a-5p exerts a seizure-suppressing effect in rats, and that SIRT1 is a direct target of miR-199a-5p in the hippocampus. The effect of miR-199a-5p on seizures and seizure damage is mediated via down-regulation of SIRT1. The miR-199a-5p/SIRT1 pathway may thus represent a potential target for the prevention and treatment of epilepsy and epileptic damage.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Targeting of microRNA‐199a‐5p protects against pilocarpine‐induced status epilepticus and seizure damage via SIRT1‐p53 cascade

Wang

Zhang

et al. 2016

Epilepsia

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“…Consistent with this, Ogawa et al (33) reported on the expression of Sirt1 in the TG of developing mice. Although several miRNAs are reported to be regulated by Sirt1, such as miR-134 in the brain (34) and miR-138 in mammalian axon regeneration (35), the spectrum of Sirt1-regulated miRNAs in diabetic TG sensory neurons remains to be explored in detail. Previous studies proposed that miR-182 was implicated in multiple functional processes, such as oncogenesis and light/dark transition in the retina (36), T helper cell clonal expansion (37), and lipid homeostasis.…”

Section: Discussionmentioning

confidence: 99%

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration

Wang

Zhao

et al. 2016

Diabetes

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Sensory neurons are particularly susceptible to neuronal damage in diabetes, and silent mating type information regulation 2 homolog 1 (Sirt1) has been recently identified as a key gene in neuroprotection and wound healing. We found that the expression of Sirt1 was downregulated in trigeminal sensory neurons of diabetic mice. A microRNA microarray analysis identified microRNA-182 (miR-182) as a Sirt1 downstream effector, and the expression level of miR-182 was increased by Sirt1 overexpression in trigeminal neurons; Sirt1 bound to the promoter of miR-182 and regulated its transcription. We also revealed that miR-182 enhanced neurite outgrowth in isolated trigeminal sensory neurons and overcame the detrimental effects of hyperglycemia by stimulating corneal nerve regeneration by decreasing the expression of one of its target genes, NOX4. Furthermore, the effects of miR-182 on corneal nerve regeneration are associated with a functional recovery of corneal sensation in hyperglycemic conditions. These data demonstrate that miR-182 is a key regulator in diabetic corneal nerve regeneration through targeting NOX4, suggesting that miR-182 might be a potential target for the treatment of diabetic sensory nerve regeneration and diabetic keratopathy.

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“…Cavalli and colleagues revealed that HDAC5 becomes exported from the nucleus following peripheral nerve injury, resulting in histone hyperacetylation and activation of a proregenerative gene expression program (16). Expression of the histone deacetylase SIRT1 was also shown to contribute to regeneration of conditioned peripheral nerve (172). Most recently, Di Giovanni's group reported that peripheral nerve injury, via ERK-mediated retrograde signaling, induces PCAF-dependent acetylation of histone H3K9 at the promoters of regeneration associated genes, triggering a transcriptional regeneration program (173).…”

Section: Importance Of Proteomics In Identifying Mechanismsmentioning

confidence: 99%

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

Niekerk

Tuszynski

et al. 2016

Molecular & Cellular Proteomics

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Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. Molecular & Cellular Proteomics

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MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

Cited by 145 publications

References 44 publications

Targeting of microRNA‐199a‐5p protects against pilocarpine‐induced status epilepticus and seizure damage via SIRT1‐p53 cascade

Targeting of microRNA‐199a‐5p protects against pilocarpine‐induced status epilepticus and seizure damage via SIRT1‐p53 cascade

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

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